Effects of MDR1 and MDR3 P-glycoproteins, MRP1, and BCRP/MXR/ABCP on the transport of 99mTc-tetrofosmin

Chen, Wendy S.; Luker, Kathryn E.; Dahlheimer, Julie L.; Pica, Christina M.; Piwnica‐Worms, David

doi:10.1016/s0006-2952(00)00341-5

Cited by 77 publications

(96 citation statements)

References 46 publications

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“…For evaluating efficacy of 5, parental human epidermal carcinoma KB-3-1 cells and their colchicine-derived KB-8-5 MDR cells [45] were used. While KB-3-1 cells do not show immunodetectable levels of Pgp, KB-8-5 MDR cells show clinically relevant expression levels of Pgp [46,47]. Therefore, these cells provided a convenient, costefficient, and reproducible in vitro system for quantitative cytotoxicity assays.…”

Section: Resultsmentioning

confidence: 99%

Metalloprobes: Synthesis, characterization, and potency of a novel gallium(III) complex in human epidermal carcinoma cells

Harpstrite

Prior

Rath

et al. 2007

Journal of Inorganic Biochemistry

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Multidrug resistance (MDR) mediated by overexpression of the MDR1 gene product, Pglycoprotein (Pgp), represents one of the best characterized barriers to chemotherapeutic treatment in cancer and may be a pivotal factor in progression of Alzheimer's disease (AD). Thus, agents capable of probing Pgp-mediated transport could be beneficial in biomedical imaging. Herein, we synthesized and structurally characterized a gallium(III) complex of the naphthol-Schiff base ligand (5). The crystal structure revealed octahedral geometry for the metallodrug. Cytotoxicity profiles of 5 were evaluated in KB-3-1 (Pgp−) and KB-8-5 (Pgp+) human epidermal carcinoma cell lines. Compared with an LC 50 (the half-maximal cytotoxic concentration) value of 1.93 μM in drug-sensitive (Pgp−) cells, the gallium(III) complex 5 demonstrated an LC 50 value > 100 μM in drug-resistant (Pgp+) cells, thus indicating that 5 was recognized by the Pgp as its substrate, thereby extruded from the cells and sequestered away from their cytotoxic targets. Radiolabeled analogues of 5 could be beneficial in noninvasive imaging of Pgp-mediated transport in vivo.

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Section: Resultsmentioning

confidence: 99%

Metalloprobes: Synthesis, characterization, and potency of a novel gallium(III) complex in human epidermal carcinoma cells

Harpstrite

Prior

Rath

et al. 2007

Journal of Inorganic Biochemistry

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“…In doxorubicin-resistant human MCF7 breast tumor cell lines, tetrofosmin uptake was much less than in wild-type drugsensitive cells [25,28]. Effects of MDR1 modulators can also be detected by TF [25,28,37]. The behavior of TF is similar to that of MIBI in functional imaging of Pgp modulation in drugresistant human cancer lines [38].…”

Section: Discussionmentioning

confidence: 99%

Imaging recognition of inhibition of multidrug resistance in human breast cancer xenografts using 99mTc-labeled sestamibi and tetrofosmin

Liu

Stevenson

Barrett

et al. 2005

Nuclear Medicine and Biology

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Background-99m Tc-sestamibi (MIBI) and 99m Tc-tetrofosmin (TF) are avid transport substrates recognized by the multidrug resistance (MDR) P-glycoprotein (Pgp). This study was designed to compare the properties of MIBI and TF in assessing the inhibition of Pgp by PSC833 in severe combined immunodeficient mice bearing MCF7 human breast tumors using SPECT imaging.Methods-Animals with drug-sensitive (MCF/WT) and drug-resistant (MCF7/AdrR) tumors were treated by PSC833 and by carrier vehicle 1 h before imaging, respectively. Dynamic images were acquired for 30 min after intravenous injection of MIBI/TF using a SPECT system, FastSPECT. The biodistribution of MIBI and TF was determined at the end of the imaging session.Results-MCF7/WT in the absence and presence of PSC833 could be visualized by MIBI and TF imaging within 5 min and remained detectable for 30 min postinjection. MCF7/AdrR could be visualized only 2-5 min without PSC833 treatment but could be detected for 30 min with PSC833, very similar to MCF7/WT. MCF7/AdrR without PSC833 showed significantly greater radioactive washout than MCF7/WT and MCF7/AdrR with PSC833 treatment. PSC833 increased the accumulation (%ID/g) in MCF7/AdrR 3.0-fold (1.62 ± 0.15 vs. 0.55 ± 0.05, P <.05) for TF and 1.9-fold (1.21 ± 0.04 vs. 0.64 ± 0.05, P <.05) for MIBI but did not affect MCF7/WT.Conclusions-The feasibility of MIBI and TF for assessment of MDR expression and inhibition was demonstrated in mice through FastSPECT imaging. The results indicate that TF may be at least comparable with MIBI in recognizing Pgp expression and modulation.

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“…Higher 99m Tc-MIBI uptake was demonstrated to correlate with biological markers of malignancy of malignant gliomas, including aneuploidy level and percentage of cells in the S-phase fraction, and with proliferative activities of glioma as assessed by the means of Ki-67 (26,27). In the majority of previous studies, tracer uptake was evaluated using the L/N ratio; the most widely used index for semi-quantitative evaluation of brain SPECT results.…”

Section: Overall Survival -------------------------------------------mentioning

confidence: 95%

Perioperative single photon emission computed tomography in predicting survival of malignant glioma patients

et al. 2012

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Abstract. Single photon emission computed tomography (SPECT) is widely used in the evaluation of glioma patients and has been demonstrated to correlate with glioma malignancy and proliferation indexes. The aim of this study was to evaluate the association between perioperative technetium-99m-methoxyisobutylisonitrile ( 99m Tc-MIBI) uptake on SPECT scans and survival of malignant glioma patients. A total of 17 patients (11 males and 6 women; mean age, 62.2±8.4 years) with histologically confirmed malignant gliomas (16 glioblastoma multiforme and 1 gliosarcoma) underwent 99m Tc-MIBI SPECT scans 2.8±1.9 days before surgery and 9.8±1.5 days after surgery. The total intensity index (TII) that corresponds to the area and intensity of tracer uptake was calculated before and after surgery. In addition, the change of TII before versus after surgery (Δ TII) was calculated. The overall survival (OS) was defined as the period between the date of surgery and the date of death. The median overall survival time was 12.4 months, ranging from 1.4 to 88 months; there were nine (45%) 12-month survivors. In univariate analyses using a log-rank test, worse OS was significantly associated with higher preoperative TII (≥12), higher postoperative TII (≥6), lower Δ TII (<50%) and higher number of neurological symptoms prior to surgery (≥4). In multivariate analyses, higher postoperative TII, a greater number of neurological symptoms and female gender were found to be factors with independent prognostic value of OS. Patients who survived more than 12 months following surgery had a significantly lower postoperative TII, higher Δ TII and greater rate of gross total resection compared to patients who survived less than 12 months following surgery. Higher perioperative tracer uptake and lower decrease of tracer uptake following surgery (suggesting less radical resection) were associated with worse OS of malignant glioma patients. Our results suggest that SPECT may be used to predict survival of malignant glioma patients; however, further studies using larger samples are required.

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Effects of MDR1 and MDR3 P-glycoproteins, MRP1, and BCRP/MXR/ABCP on the transport of 99mTc-tetrofosmin

Cited by 77 publications

References 46 publications

Metalloprobes: Synthesis, characterization, and potency of a novel gallium(III) complex in human epidermal carcinoma cells

Metalloprobes: Synthesis, characterization, and potency of a novel gallium(III) complex in human epidermal carcinoma cells

Imaging recognition of inhibition of multidrug resistance in human breast cancer xenografts using 99mTc-labeled sestamibi and tetrofosmin

Perioperative single photon emission computed tomography in predicting survival of malignant glioma patients

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